Research Interests

Two research projects are ongoing in my Neuroprotection and Drug Abuse Research Lab:

The first project is dealing with the investigation of the role of glutamate transport
in alcohol dependence. While it has been clearly established that dopaminergic neurotransmission
plays an important role in reward and drug addiction, increasing evidence suggests
that many aspects of the plasticity of drug addiction involves changes in glutamatergic
neurotransmission. I have recently identified an FDA-approved drug and other related
compounds that can cross the brain blood barrier and facilitate glutamate neurotransmission.
We have tested one of these drugs and found potential therapeutic effects in a model
of drug abuse such as cocaine addiction. Our ongoing research projects focused on
the identification and pharmacological studies of drugs known to upregulate the glutamate
transporter 1 (termed also excitatory amino acid transporter 2, EAAT2) and their role
for the treatment of alcohol dependence. We use animal model of alcohol dependence
to determine the behavioral, molecular and pharmacological manipulations of all these
therapeutic drugs. This project is currently funded by the National Institutes of
Health-NIAAA (R01).

The second project is dealing with the use of derived neurotrophic peptides and other
neuroprotective compounds in the treatment of diseases involving oxidative stress.
Oxidative stress is the major cause for most of neurodegenerative diseases. We have
tested the role of neurotrophic factors in a model of oxidative stress involving alcohol
exposure in brain development and have shown neuroprotective effects. We have demonstrated
that derived neurotrophic peptides prevent alcohol-induced mitochondrial dysfunction.
Mitochondrion is a key play in oxidative stress, thus preventing its dysfunction will
be a therapeutic useful tool to prevent or delay the progression of neurodegenerative
diseases. Since my lab is focusing in Huntington’s disease, we are currently working
in testing these novel trophic factors to prevent or slow the progression of the disease.
We are using transgenic mice. that have the dysfunctional human huntingtin protein.
We are also testing other compounds that have anti-oxidative effects. We aim to delineate
the precise signaling pathways that mediate these trophic factors and other anti-oxidative
compounds in neuroprotection using Huntington’s disease mouse models.

Y. Sari, V. R. Johnson, J.M. Weedman. Role of the serotonergic system in alcohol-drinking
behavior: from animal models to clinics. In The Brain as a Drug Target, volume 98, Progress in Molecular Biology and Translational Science, (2011), pages 401-443.